Efficacy and safety of nilotinib 300 mg twice daily in patients with chronic myeloid leukemia in chronic phase who are intolerant to prior tyrosine kinase inhibitors: Results from the Phase IIIb ENESTswift study

Devendra Hiwase, Peter Tan, James D'Rozario, John Taper, Anthony Powell, Ian Irving, Matthew Wright, Susan Branford, David T. Yeung, Luke Anderson, Othon Gervasio, Carly Levetan, Will Roberts, Ann Solterbeck, Robert Traficante, Timothy Hughes

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background: Some patients receiving a tyrosine kinase inhibitor (TKI) for the first-line treatment of chronic phase chronic myeloid leukemia (CML-CP) experience intolerable adverse events. Management strategies include dose adjustments, interrupting or discontinuing therapy, or switching to an alternative TKI. Methods: This multicenter, single-arm, Phase IIIb study included CML-CP patients intolerant of, but responsive to, first-line treatment with imatinib or dasatinib. All patients were switched to nilotinib 300 mg bid for up to 24 months. The primary endpoint was achievement of MR4.5 (BCR-ABL transcript level of ≤0.0032% on the International Scale) by 24 months. Results: Twenty patients were enrolled in the study (16 imatinib-intolerant, 4 dasatinib-intolerant); which was halted early because of low recruitment. After the switch to nilotinib 300 mg bid, MR4.5 at any time point up to month 24 was achieved in 10 of 20 patients (50%) in the full analysis set. Of the non-hematological adverse events associated with intolerance to prior imatinib or dasatinib, 74% resolved within 12 weeks of switching to nilotinib 300 mg bid. Conclusion: Nilotinib 300 mg bid shows minimal cross intolerance in patients with CML-CP who have prior toxicities to other TKIs and can lead to deep molecular responses.

LanguageEnglish
Pages109-115
Number of pages7
JournalLeukemia Research
Volume67
DOIs
Publication statusPublished - 1 Apr 2018

Keywords

  • Chronic myeloid leukemia
  • Nilotinib
  • Tyrosine kinase inhibitor

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Hiwase, Devendra ; Tan, Peter ; D'Rozario, James ; Taper, John ; Powell, Anthony ; Irving, Ian ; Wright, Matthew ; Branford, Susan ; Yeung, David T. ; Anderson, Luke ; Gervasio, Othon ; Levetan, Carly ; Roberts, Will ; Solterbeck, Ann ; Traficante, Robert ; Hughes, Timothy. / Efficacy and safety of nilotinib 300 mg twice daily in patients with chronic myeloid leukemia in chronic phase who are intolerant to prior tyrosine kinase inhibitors : Results from the Phase IIIb ENESTswift study. In: Leukemia Research. 2018 ; Vol. 67. pp. 109-115.
@article{411e6532677f45e3b68ac32d4eff9384,
title = "Efficacy and safety of nilotinib 300 mg twice daily in patients with chronic myeloid leukemia in chronic phase who are intolerant to prior tyrosine kinase inhibitors: Results from the Phase IIIb ENESTswift study",
abstract = "Background: Some patients receiving a tyrosine kinase inhibitor (TKI) for the first-line treatment of chronic phase chronic myeloid leukemia (CML-CP) experience intolerable adverse events. Management strategies include dose adjustments, interrupting or discontinuing therapy, or switching to an alternative TKI. Methods: This multicenter, single-arm, Phase IIIb study included CML-CP patients intolerant of, but responsive to, first-line treatment with imatinib or dasatinib. All patients were switched to nilotinib 300 mg bid for up to 24 months. The primary endpoint was achievement of MR4.5 (BCR-ABL transcript level of ≤0.0032{\%} on the International Scale) by 24 months. Results: Twenty patients were enrolled in the study (16 imatinib-intolerant, 4 dasatinib-intolerant); which was halted early because of low recruitment. After the switch to nilotinib 300 mg bid, MR4.5 at any time point up to month 24 was achieved in 10 of 20 patients (50{\%}) in the full analysis set. Of the non-hematological adverse events associated with intolerance to prior imatinib or dasatinib, 74{\%} resolved within 12 weeks of switching to nilotinib 300 mg bid. Conclusion: Nilotinib 300 mg bid shows minimal cross intolerance in patients with CML-CP who have prior toxicities to other TKIs and can lead to deep molecular responses.",
keywords = "Chronic myeloid leukemia, Nilotinib, Tyrosine kinase inhibitor",
author = "Devendra Hiwase and Peter Tan and James D'Rozario and John Taper and Anthony Powell and Ian Irving and Matthew Wright and Susan Branford and Yeung, {David T.} and Luke Anderson and Othon Gervasio and Carly Levetan and Will Roberts and Ann Solterbeck and Robert Traficante and Timothy Hughes",
year = "2018",
month = "4",
day = "1",
doi = "10.1016/j.leukres.2018.02.013",
language = "English",
volume = "67",
pages = "109--115",
journal = "Leukemia Research",
issn = "0145-2126",
publisher = "Elsevier Limited",

}

Efficacy and safety of nilotinib 300 mg twice daily in patients with chronic myeloid leukemia in chronic phase who are intolerant to prior tyrosine kinase inhibitors : Results from the Phase IIIb ENESTswift study. / Hiwase, Devendra; Tan, Peter; D'Rozario, James; Taper, John; Powell, Anthony; Irving, Ian; Wright, Matthew; Branford, Susan; Yeung, David T.; Anderson, Luke; Gervasio, Othon; Levetan, Carly; Roberts, Will; Solterbeck, Ann; Traficante, Robert; Hughes, Timothy.

In: Leukemia Research, Vol. 67, 01.04.2018, p. 109-115.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Efficacy and safety of nilotinib 300 mg twice daily in patients with chronic myeloid leukemia in chronic phase who are intolerant to prior tyrosine kinase inhibitors

T2 - Leukemia Research

AU - Hiwase, Devendra

AU - Tan, Peter

AU - D'Rozario, James

AU - Taper, John

AU - Powell, Anthony

AU - Irving, Ian

AU - Wright, Matthew

AU - Branford, Susan

AU - Yeung, David T.

AU - Anderson, Luke

AU - Gervasio, Othon

AU - Levetan, Carly

AU - Roberts, Will

AU - Solterbeck, Ann

AU - Traficante, Robert

AU - Hughes, Timothy

PY - 2018/4/1

Y1 - 2018/4/1

N2 - Background: Some patients receiving a tyrosine kinase inhibitor (TKI) for the first-line treatment of chronic phase chronic myeloid leukemia (CML-CP) experience intolerable adverse events. Management strategies include dose adjustments, interrupting or discontinuing therapy, or switching to an alternative TKI. Methods: This multicenter, single-arm, Phase IIIb study included CML-CP patients intolerant of, but responsive to, first-line treatment with imatinib or dasatinib. All patients were switched to nilotinib 300 mg bid for up to 24 months. The primary endpoint was achievement of MR4.5 (BCR-ABL transcript level of ≤0.0032% on the International Scale) by 24 months. Results: Twenty patients were enrolled in the study (16 imatinib-intolerant, 4 dasatinib-intolerant); which was halted early because of low recruitment. After the switch to nilotinib 300 mg bid, MR4.5 at any time point up to month 24 was achieved in 10 of 20 patients (50%) in the full analysis set. Of the non-hematological adverse events associated with intolerance to prior imatinib or dasatinib, 74% resolved within 12 weeks of switching to nilotinib 300 mg bid. Conclusion: Nilotinib 300 mg bid shows minimal cross intolerance in patients with CML-CP who have prior toxicities to other TKIs and can lead to deep molecular responses.

AB - Background: Some patients receiving a tyrosine kinase inhibitor (TKI) for the first-line treatment of chronic phase chronic myeloid leukemia (CML-CP) experience intolerable adverse events. Management strategies include dose adjustments, interrupting or discontinuing therapy, or switching to an alternative TKI. Methods: This multicenter, single-arm, Phase IIIb study included CML-CP patients intolerant of, but responsive to, first-line treatment with imatinib or dasatinib. All patients were switched to nilotinib 300 mg bid for up to 24 months. The primary endpoint was achievement of MR4.5 (BCR-ABL transcript level of ≤0.0032% on the International Scale) by 24 months. Results: Twenty patients were enrolled in the study (16 imatinib-intolerant, 4 dasatinib-intolerant); which was halted early because of low recruitment. After the switch to nilotinib 300 mg bid, MR4.5 at any time point up to month 24 was achieved in 10 of 20 patients (50%) in the full analysis set. Of the non-hematological adverse events associated with intolerance to prior imatinib or dasatinib, 74% resolved within 12 weeks of switching to nilotinib 300 mg bid. Conclusion: Nilotinib 300 mg bid shows minimal cross intolerance in patients with CML-CP who have prior toxicities to other TKIs and can lead to deep molecular responses.

KW - Chronic myeloid leukemia

KW - Nilotinib

KW - Tyrosine kinase inhibitor

UR - http://www.scopus.com/inward/record.url?scp=85042510946&partnerID=8YFLogxK

U2 - 10.1016/j.leukres.2018.02.013

DO - 10.1016/j.leukres.2018.02.013

M3 - Article

VL - 67

SP - 109

EP - 115

JO - Leukemia Research

JF - Leukemia Research

SN - 0145-2126

ER -